Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy

Autor: Michaela Liedtke, Amarendra K. Neppalli, Elizabeth McGehee, Ehsan Malek, Saad Z. Usmani, Robert F. Cornell, Swapna Narayana, Ankit Kansagra, Natalie S. Callander, Elvira Umyarova, Parameswaran Hari, Arjun Lakshman, Ridhi Gupta, Barry Paul, Joshua Mansour, Zhubin Gahvari, Ujjawal H. Gandhi, William Varnado, Alyssa Barnstead, Saurabh Chhabra, Mark A. Fiala, Emma C. Scott, Megan Jagosky, Saranya Kodali, Ravi Vij, Yubin Kang, Kelly N. Godby, Luciano J. Costa, Shaji Kumar
Rok vydání: 2019
Předmět:
Adult
Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Population
Antibodies
Monoclonal
Humanized
Article
Cohort Studies
Young Adult
03 medical and health sciences
chemistry.chemical_compound
Antineoplastic Agents
Immunological
0302 clinical medicine
Refractory
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Immunologic Factors
Progression-free survival
education
Multiple myeloma
Aged
Aged
80 and over
Isatuximab
education.field_of_study
Membrane Glycoproteins
business.industry
Antibodies
Monoclonal
Daratumumab
Hematology
Middle Aged
medicine.disease
ADP-ribosyl Cyclase 1
Carfilzomib
Progression-Free Survival
Regimen
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Female
Immunotherapy
Multiple Myeloma
business
Proteasome Inhibitors
Zdroj: Leukemia. 33:2266-2275
ISSN: 1476-5551
0887-6924
DOI: 10.1038/s41375-019-0435-7
Popis: The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to CD38 MoABs. Median interval between MM diagnosis and refractoriness to CD38 MoAB (T(0)) was 50.1 months. The median overall survival (OS) from T(0) for the entire cohort was 8.6 [95% C.I. 7.5–9.9] months, ranging from 11.2 months for patients not simultaneously refractory to an immunomodulatory (IMiD) agent and a proteasome inhibitor (PI) to 5.6 months for “penta-refractory” patients (refractory to CD38 MoAB, 2 PIs and 2 IMiDs). At least one subsequent treatment regimen was employed after T(0) in 249 (90%) patients. Overall response rate to first regimen after T(0) was 31% with median progression-free survival (PFS) and OS of 3.4 and 9.3 months, respectively. PFS was best achieved with combinations of carfilzomib and alkylator (median 5.7 months), and daratumumab and IMiD (median 4.5 months). Patients with MM refractory to CD38 MoAB have poor prognosis and this study provides benchmark for new therapies to be tested in this population.
Databáze: OpenAIRE
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